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1 Journal Of Scientific Research in Allied Sciences ISSN NO Contents available at: EVALUATION OF NEUROENDOCRINE TUMOR FREQUENCY AND PREDICTIVE VALUE OF NEUTROPHIL-LYMPHOCYTE RATIO IN ACUTE APPENDICITIS CASES Mehmet Ilker Turan 1, Mehmet Celik 2, Mehmet Akif Turkoglu 3, Direnc Yigit 4 1 Antalya Kepez State Hospital, Department of General Surgery, Antalya, Turkey 2 Antalya Kepez State Hospital, Department of Endocrinology and Metabolism, Antalya, Turkey 3 Gazi University Faculty of Medicine, Department of General Surgery, Ankara, Turkey 4 Abant İzzet Baysal University Faculty of Medicine, Department of General Surgery, Division of Gastroenterology Surgery, Bolu, Turkey ARTICLE INFO ABSTRACT ORIGINAL RESEARCH ARTICLE Article History Received: Dec 2018 Accepted: Jan 2019 Keywords: Appendicitis; neutrophillymphocyte ratio; perforation Corresponding author Mehmet Celik* Objective: The aim of this study was to investigate the efficacy of simple accessible laboratory parameters such as neutrophil-lymphocyte ratio (NLR) in the diagnosis of acute appendicitis and the incidence of neuroendocrine tumors in patients operated with an initial diagnosis of acute appendicitis. Materials and methods: Postoperative pathology diagnosis, neutrophillymphocyte ratio, age, sex, perforation of 952 patients with an initial diagnosis of acute appendicitis between January 2009 and December 2015 were reviewed retrospectively. Acute appendicitis cases were divided into two groups as complicated (perforated) and simple uncomplicated cases. NLR ratio was calculated. Receiver operating characteristic (ROC) curve analysis was used to define important parameters in multivariate analysis. Cut-off values, sensitivity, specificity and accuracy calculations were made for the parameters under the curve area (AUC)> Results: 23 patients were excluded from the study due to incomplete data. Normal appendix in 1 (0.1%), endometriosis in 1 (0.1%), adenocarcinoma in 4 (0.4%) cases, neuroendocrine tumor in 7 (0.8%) cases, lymphoid hyperplasia in 138 (14.9%) cases and acute appendicitis was detected in 778 (83.7%) cases. Of the 778 patients, 124 (15.9%) had a perforation. NLR sensitivity and specificity were found in cases with acute appendicitis but not in complicated cases. However, the cut-off point of NLR with sensitivity of 85% and a specificity of 94% was found to be> 4,526 in the complicated acute appendicitis. Conclusion: NLR> in subjects with perforation was found to be significantly associated with acute appendicitis. 2019, INTRODUCTION Appendicitis is one of the most common causes of acute abdominal pain. It is one of the most common indications for abdominal surgery worldwide (1, 2). Appendicitis often occurs in the 2nd and 3rd decades. It is 1.4 times more common in males than in females [3]. Appendiceal 1 P a g e
2 obstruction can be due to fecalite, lymphoid hyperplasia, infectious conditions and tumors (4, 5). Among the laboratory findings of patients with acute appendicitis, a mild leukocytosis is the most common (6). Approximately 80% of patients have leftsided gliding with neutrophil predominance with leukocytosis. In patients with acute appendicitis, the high WBC count has a sensitivity of 80% and a specificity of 55 (7-9). In addition, the mean number of WBCs increased in patients with gangrenous or perforated acute appendicitis compared to the other cases (10). MATERIAL AND METHODS: Postoperative pathology diagnosis, neutrophil-lymphocyte ratio, age, sex, and perforation were evaluated retrospectively in 952 patients with an initial diagnosis of acute appendicitis between January 2009 and December cases were excluded from the study due to missing data. Patients with acute appendicitis with perforation were divided into two groups as uncomplicated, uncomplicated cases. Demographic data, preoperative WCC, neutrophil count, lymphocyte count, NLR were calculated. Postoperative histopathological diagnoses were recorded. ROC curve analysis was used to define important parameters in multivariate analysis. Cut-off values, sensitivity, specificity and accuracy calculations were made for the parameters under the curve area (AUC)> RESULTS: The histopathological results of 929 patients were normal appendix in 1 (0.1%), endometriosis in 1 (0.1%), adenocarcinoma in 4 (0.4%), neuroendocrine tumor in 7 (0.8%), lymphoid hyperplasia in 138 (14.9%), 778 (83.7%) had acute appendicitis. The mean age of 778 patients with acute appendicitis was ± Of the patients, 316 (40.6%) were females while 462 (59.4%) were males. Of the 778 patients, 124 (15.9%) had a perforation. In the case of uncomplicated acute appendicitis cases, the area under the curve was Also, since the sensitivity and specificity were low as the likelihood ratio <2, a certain cut off value was not considered for NLR (figure 1). Figure 1. Roc curve analysis in patients with uncomplicated acute appendicitis In the cases of complicated acute appendicitis, the area under the curve was Since the likelihood ratio was> 2, the cutoff value was determined for NLR. The 2 P a g e
3 cut-off value for NLR was found to be with 85% sensitivity and 94% specificity in complicated acute appendicitis cases. Figure 2. Roc curve analysis in patients with perforated acute appendicitis. Table 1. Histopathological and demographic data in patients who were operated with the diagnosis of acute appendicitis. Histopathological Gender n(%) Perforation n(%) Total diagnosis Female Male Negative Positive Appendicitis (40.6 %) (59.4%) (84.1%) (15.9%) Lymphoid Hyperplasia (37%) (63.%) (90.6%) (9.4%) Adenocarcinoma 3 (75%) 1 (25%) 4 (100%) 0 (0%) 4 Neuroendocrine 2 (28.6%) 5 (71.4%) 6 (85.7%) 1 (14.3%) 7 tumor Endometriosis 1 (100%) 0 (0%) 1 (100%) 0 (0%) 1 Normal 0 (0%) 1 (100%) 1 (100%) 0 (0%) 1 Total 373 (40.2%) 556 (59.8%) 791 (85.1%) 138 (14.9%) 929 DISCUSSION Most of the patients who underwent abdominal surgery for acute abdomen still have acute appendicitis in the world in the etiology (1-2). In acute appendicitis cases, it may cause acute abdominal disease by causing obstruction in benign or malign tumors except for infectious process. In our study, 4 (0.4%) cases had adenocarcinoma and 7 (0.8%) patients had neuroendocrine tumor appendicitis. In less than 3% of patients undergoing an appendectomy, 3 P a g e
4 carcinoid tumor with primary appendix tumor, goblet cell carcinoma, lymphoma, mucocele, primary adenocarcinoma, and mucinous cyst are adenocarcinomas. A carcinoid tumor is the most common primary appendix tumor. They develop from enterochromaffin or Kulchitsky cells of the neuroendocrine system. The incidence of carcinoid tumor was %. It is more common in women (11-14). In our study, the mean age of cases with carcinoid tumor was ± 9. Five (71%) of the patients were males while 2 (29%) were females. Appendix carcinoid tumors are often incidental with an appendectomy. It is very difficult to diagnose during surgery without histopathological examination. For the diagnosis of acute appendicitis, the experience of the examiner is the most important factor. In addition, ultrasound, computed tomography or MR imaging improve the sensitivity of the diagnosis (15-17). However, in some cases, the physician may not have the possibility of radiological imaging. The aim of this study is to evaluate the cheaper, more easily accessible NLR ratio. Kahramanca et al. (18) reported a high likelihood ratio of acute appendicitis in patients with a cut-off value of> 4.68 in NLR. Goodman et al. (19) reported that in 298 patients with appendicitis, NLR> 3.5 would increase the sensitivity in the diagnosis. Yazici et al. (20) reported a high likelihood ratio of acute appendicitis in patients with a cut-off value of NLR> 3.5. In our study, roc curve analysis for NLR was found to be low in uncomplicated acute appendicitis cases. In cases with complicated acute appendicitis, the cut-off value was determined by calculating the likelihood ratio for NLR> 2. The cut-off value for NLR was found to be with 85% sensitivity and 94% specificity in complicated acute appendicitis cases. Ishizuka et al. (21) argued that gangrenous appendicitis is important in patients who underwent appendectomy with a neutrophillymphocyte ratio> 8. CONCLUSION Laboratory parameter NLR> 4.526; since it is easily accessible, cost-effective, it has a reliable likelihood ratio in the diagnosis of complicated cases with acute appendicitis. More work is needed to use NLR in clinical practice. Conflict of Interest: No conflict of interest was declared by the authors. Financial Disclosure: The authors declared that this study received no financial support. REFERENCES 1. Williams GR. Presidential Address: a history of appendicitis. With anecdotes illustrating its importance. Ann Surg 1983; 197: Fitz RH. Perforating inflammation of the vermiform appendix with special reference to its early diagnosis and treatment. Am J Med Sci 1886; 92: Addiss DG, Shaffer N, Fowler BS, Tauxe RV. The epidemiology of appendicitis and appendectomy in the United States. Am J Epidemiol 1990; 132: Nitecki S, Karmeli R, Sarr MG. Appendiceal calculi and fecaliths as indications for the appendectomy. Surg Gynecol Obstet 1990; 171: Jones BA, Demetriades D, Segal I, Burkitt DP. The prevalence of appendiceal fecaliths in patients with and without appendicitis. A comparative study from Canada and South Africa. Ann Surg 1985; 202: Cope Z, Silen W. Cope's Early Diagnosis of the Acute Abdomen, 19th ed, Oxford University Press, New York p Coleman C, Thompson JE Jr, Bennion RS, Schmit PJ. White blood cell count is a poor predictor of severity of disease in the diagnosis of appendicitis. Am Surg 1998; 64: P a g e
5 8. Tehrani HY, Petros JG, Kumar RR, Chu Q. Markers of severe appendicitis. Am Surg 1999; 65: Thompson MM, Underwood MJ, Dookeran KA, et al. Role of sequential leucocyte counts and C-reactive protein measurements in acute appendicitis. Br J Surg 1992; 79: Guraya SY, Al-Tuwaijri TA, Khairy GA, Murshid KR. The validity of leukocyte count to predict the severity of acute appendicitis. Saudi Med J 2005; 26: Ma KW, Chia NH, Yeung HW, Cheung MT. If not appendicitis, then what else can it be? A retrospective review of 1492 appendectomies. Hong Kong Med J 2010;16(1): Connor SJ, Hanna GB, Frizelle FA. Appendiceal tumors: retrospective clinicopathologic analysis of appendiceal tumors from 7,970 appendectomies. Dis Colon Rectum 1998;41(1): Modlin IM, Lye KD, Kidd M. A 5- decade analysis of 13,715 carcinoid tumors. Cancer 2003;97(4): Bucher P, Mathe Z, Demirag A, Morel P. Appendix tumors in the era of laparoscopic appendectomy. Surg Endosc 2004;18(7): Kosloske AM, Love CL, Rohrer JE, et al. The diagnosis of appendicitis in children: outcomes of a strategy based on the pediatric surgical evaluation. Pediatrics 2004; 113: Kharbanda AB, Fishman SJ, Bachur RG. Comparison of pediatric emergency physicians' and surgeons' evaluation and diagnosis of appendicitis. Acad Emerg Med 2008; 15: Smith MP, Katz DS, Lalani T, et al. ACR Appropriateness Criteria Right Lower Quadrant Pain--Suspected Appendicitis. Ultrasound Q 2015; 31: Kahramanca S, Ozgehan G, Seker D, Gökce EI, Seker G, Tunç G, Küçükpınar T, Kargıcı H. Neutrophil-to-lymphocyte ratio as a predictor of acute appendicitis. Ulus Travma Acil Cerrahi Derg Jan;20(1): Goodman DA, Goodman CB, Monk JS. Use of the neutrophil: lymphocyte ratio in the diagnosis of appendicitis. Am Surg 1995;61: Yazici M, Ozkisacik S, Oztan MO, Gürsoy H. Neutrophil/lymphocyte ratio in the diagnosis of childhood appendicitis. Turk J Pediatr 2010;52: [1]. Ishizuka M, Shimizu T, Kubota K. Neutrophil-to-Lymphocyte Ratio Has a Close Association With Gangrenous Appendicitis in Patients Undergoing Appendectomy. Int Surg 2012;97: P a g e
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